The lead and cadmium content in rice and risk to human health in China: A systematic review and meta-analysis

Numerous studies have investigated concentrations of lead (Pb) and cadmium (Cd) in rice in China, but have come to divergent conclusions. Therefore we systematically reviewed and meta-analyzed the available evidence on levels of Pb and Cd in rice in different regions of China in order to assess the potential risk to human health. The meta-analysis included 24 studies of Pb levels and 29 studies of Cd levels, published in 2011–2021. The pooled Pb concentration in rice was 0.10 mg per kg dry weight (95% CI 0.08−0.11), while the pooled Cd concentration was 0.16 mg per kg dry weight (95% CI 0.14−0.18). These levels are within the limits specified by national food safety standards. However, the total target hazard quotient for both metals exceeded 1.0 for adults and children, suggesting that rice consumption poses a health risk.

sure it is accurate.  The authors have declared that no competing interests exist. NO  Numerous studies have investigated concentrations of lead (Pb) and cadmium (Cd) in 24 rice in China, but have come to divergent conclusions. Therefore we systematically 25 reviewed and meta-analyzed the available evidence on levels of Pb and Cd in rice in 26 different regions of China in order to assess the potential risk to human health. The 27 meta-analysis included 24 studies of Pb levels and 29 studies of Cd levels, published in 28 2011-2021. The pooled Pb concentration in rice was 0.10 mg per kg dry weight (95% 29 CI 0.08−0.11), while the pooled Cd concentration was 0.16 mg per kg dry weight (95% 30 CI 0.14−0.18). These levels are within the limits specified by national food safety 31 standards. However, the total target hazard quotient for both metals exceeded 1.0 for 32 adults and children, suggesting that rice consumption poses a health risk. 33

Introduction 37
Rice is a well-known staple food, consumed by about 50% of the population in more 38 than 100 countries around the world. As the most populous country in the world, China 39 is the largest producer and consumer of rice in the world. China's annual rice production 40 totals approximately 2.07 × 10 11 kg and accounts for nearly 34% of total global output 41 for all outcomes. Statistical heterogeneity among studies was assessed based on I 2 , with 106 25% defined as low heterogeneity; 50%, moderate heterogeneity; and 75%, high 107 heterogeneity (31, 32). Meta-analysis was performed using a random-effects model if 108 I 2 > 50% (33); otherwise, a fixed-effect model was used. Meta-regression was used to 109 identify studies that might explain the observed heterogeneity; the covariates in this 110 regression were years of sampling, study area, assay method, sample size, and quality 111 score. Sources of heterogeneity were also explored through meta-analysis of subgroups 112 defined by years of sampling, study area, assay method, sample size and quality score. 113 114 Sensitivity analysis was conducted by omitting studies one by one, and the P values of 115 pooled concentrations were compared. The results were considered robust if the P 116 values were not substantially different. Publication bias was quantitatively analyzed 117 using Egger's test (34), and risk of bias was considered significant if P < 0.05. 118 119 Health risk assessment 120 The target hazard quotient (THQ) developed by the US Environmental Protection 121 Agency (35) was used to assess the potential human health risks associated with long-122 term exposure to heavy metal pollutants in rice. The THQ was calculated as 123  in the analysis (Fig. 1). 145 146

Study characteristics 147
The main characteristics of the 30 studies are presented in Table 1

Assessment of study quality 158
All studies in the review were judged to be of high or medium quality according to the 159 Combie evaluation tool. The average score was 6.2 points, with 75.9% of the included 160 studies scoring greater than 5.5 points (Table 1). 161 162

Meta-regression analysis 185
Both uni-and multivariate meta-regressions were conducted with the following 186 covariates: years of sampling, area, assay method, sample size and quality score. 187 Univariate meta-regression for Pb showed that years of sampling, area, assay method, 188 sample size and quality score did not affect outcomes (Table 2). Nevertheless, assay 189 method could explain 16.03% of heterogeneity (adjusted R 2 = 16.03 %, P = 0.046). 190 None of the factors tested substantially affected multivariate meta-regression (Table 3). and sample size (adjusted R 2 = 15.56%, P = 0.016; Table 4). In contrast, years of 197 sampling, assay method and quality score did not affect outcomes. Multivariate meta-198 regression showed that years of sampling, central vs non-central China, assay method, 199 sample size and quality score were able to explain 41.86% of heterogeneity (Table 5).   (Table 7).  (Table  238 6). Pooled concentrations of Cd (mg/kg) were 0.12 (95%CI 0.10, 0.14) among small 239 studies and 0.27 (95%CI 0.21, 0.33) among large studies (Table 7). 240 241 Among studies measuring Pb, 18 were assigned to high quality and gave a pooled 242 concentration of 0.10 (95%CI 0.08, 0.11) mg/kg. Four studies were assigned to medium 243 quality and gave a pooled concentration of 0.13 (95%CI -0.05, 0.30) mg/kg (Table 6). 244 Among studies measuring Cd, 24 were assigned to high quality and gave a pooled 245 concentration of 0.19 (95%CI 0.17, 0.21) mg/kg. Nine studies were assigned to medium 246 quality and gave a pooled concentration of 0.09 (95%CI 0.05, 0.13) mg/kg (Table 7). 247 248 Our meta-analysis indicated more serious contamination of rice with Cd than with Pb. 249 Contamination with Cd appears particularly severe in the central region of China (0.43 250 mg/kg), based primarily on pooled data from Hunan (11, 40-44) but also some data 251  (Table 8), both of which are below 1.0, indicating safe levels in rice. In contrast, 265 the Cd THQ was 1.11 for adults and 0.97 for children, indicating a health concern for 266 adults but not children. Combining the THQs for Pb and Cd led to a total THQ higher 267 than 1 for adults and children. This suggests a serious health risk for children and adults.               Regions of China are defined as in Table 2. indicates exceed the standard limit.